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Protein

DNA demethylase ALKBH1

Gene

ALKBH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dioxygenase that acts as a DNA demethylase (PubMed:18603530). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:18603530). Specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA. N(6)-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (By similarity). Also able to repair alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation, but with low activity (PubMed:18603530). Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (PubMed:19959401). DNA lyase activity does not require alpha-ketoglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (PubMed:19959401, PubMed:23577621). DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. May play a role in placental trophoblast lineage differentiation (By similarity).By similarity3 Publications

Catalytic activityi

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.1 Publication
DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.1 Publication
N(6)-methyladenine in DNA + 2-oxoglutarate + O2 = adenine in DNA + formaldehyde + succinate + CO2.By similarity

Cofactori

Fe2+PROSITE-ProRule annotation1 PublicationNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei133Primary catalytic residue forming the imine linkage with DNA1 Publication1
Sitei133Secondary catalytic residue forming the imine linkage with DNA1 Publication1
Binding sitei144SubstrateBy similarity1
Metal bindingi231Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi233Iron; catalyticPROSITE-ProRule annotation1
Binding sitei233SubstrateBy similarity1
Metal bindingi287Iron; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • 1-ethyladenine demethylase activity Source: UniProtKB-EC
  • chemoattractant activity Source: Ensembl
  • DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
  • ferrous iron binding Source: UniProtKB
  • methylcytosine dioxygenase activity Source: UniProtKB

GO - Biological processi

  • developmental growth Source: Ensembl
  • DNA dealkylation involved in DNA repair Source: UniProtKB
  • DNA demethylation Source: UniProtKB
  • DNA repair Source: UniProtKB
  • in utero embryonic development Source: Ensembl
  • negative regulation of neuron apoptotic process Source: Ensembl
  • neuron migration Source: Ensembl
  • neuron projection development Source: Ensembl
  • oxidative demethylation Source: UniProtKB
  • placenta development Source: Ensembl
  • regulation of gene expression Source: Ensembl
  • RNA repair Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Lyase, Oxidoreductase

Keywords - Biological processi

DNA damage, DNA repair, RNA repair

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100601-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA demethylase ALKBH1 (EC:1.14.11.-By similarity)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 11 Publication
Alpha-ketoglutarate-dependent dioxygenase ABH11 Publication
DNA 6mA demethylaseBy similarity
DNA N6-methyl adenine demethylaseBy similarity (EC:1.14.11.-By similarity)
DNA lyase ABH11 Publication (EC:4.2.99.181 Publication)
DNA oxidative demethylase ALKBH1 (EC:1.14.11.331 Publication)
Gene namesi
Name:ALKBH1
Synonyms:ABH1 Publication, ABH11 Publication, ALKBH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:17911. ALKBH1.

Subcellular locationi

GO - Cellular componenti

  • mitochondrion Source: UniProtKB
  • nuclear euchromatin Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi25K → A: Moderate decrease in DNA lyase activity. Reduced DNA lyase activity; when associated with A-133. 1 Publication1
Mutagenesisi55K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi61K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi64K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi87K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi94K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi113H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi116K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi118C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi120K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi125K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi129C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi133K → A: Reduced DNA lyase activity. Slightly more reduced DNA lyase activity; when associated with A-25. Strongly reduced activity; when associated with A-154. 1 Publication1
Mutagenesisi134H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi137K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi148K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi154K → A: Does not affect DNA lyase activity. Strongly reduced activity; when associated with A-133. 1 Publication1
Mutagenesisi158K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi167K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi182K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi183K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi218I → L: Reduces Fe2OG dioxygenase activity by 50%. 1 Publication1
Mutagenesisi231H → A: Near loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. 2 Publications1
Mutagenesisi233D → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. 2 Publications1
Mutagenesisi241K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi287H → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. 2 Publications1
Mutagenesisi303H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi304C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi335K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi338R → A: Reduced Fe2OG dioxygenase activity. 1 Publication1
Mutagenesisi344R → A: Reduced Fe2OG dioxygenase activity. 1 Publication1
Mutagenesisi362K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi371C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi372H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi381K → A: Does not affect DNA lyase activity. 1 Publication1

Organism-specific databases

DisGeNETi8846.
OpenTargetsiENSG00000100601.
PharmGKBiPA134906996.

Polymorphism and mutation databases

BioMutaiALKBH1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000666681 – 389DNA demethylase ALKBH1Add BLAST389

Proteomic databases

EPDiQ13686.
MaxQBiQ13686.
PaxDbiQ13686.
PeptideAtlasiQ13686.
PRIDEiQ13686.

PTM databases

iPTMnetiQ13686.
PhosphoSitePlusiQ13686.

Expressioni

Tissue specificityi

Ubiquitous.2 Publications

Gene expression databases

BgeeiENSG00000100601.
CleanExiHS_ALKBH1.
ExpressionAtlasiQ13686. baseline and differential.
GenevisibleiQ13686. HS.

Organism-specific databases

HPAiHPA044087.

Interactioni

Subunit structurei

Monomer (PubMed:19959401). Interacts with DNAJB6 (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi114372. 1 interactor.
STRINGi9606.ENSP00000216489.

Structurei

3D structure databases

ProteinModelPortaliQ13686.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini208 – 347Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST140

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 177Substrate bindingBy similarity3
Regioni220 – 222Alpha-ketoglutarate bindingBy similarity3
Regioni338 – 344Alpha-ketoglutarate bindingBy similarity7

Sequence similaritiesi

Belongs to the alkB family.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2731. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00390000004599.
HOGENOMiHOG000033905.
HOVERGENiHBG050487.
InParanoidiQ13686.
KOiK10765.
OMAiGFCHLDD.
OrthoDBiEOG091G0A10.
PhylomeDBiQ13686.
TreeFamiTF314609.

Family and domain databases

Gene3Di2.60.120.590. 2 hits.
InterProiIPR004574. Alkb.
IPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR16557. PTHR16557. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00568. alkb. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q13686-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH
60 70 80 90 100
AARGKGPGAQ KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI
110 120 130 140 150
FIPNPFLPGY QWHWVKQCLK LYSQKPNVCN LDKHMSKEET QDLWEQSKEF
160 170 180 190 200
LRYKEATKRR PRSLLEKLRW VTVGYHYNWD SKKYSADHYT PFPSDLGFLS
210 220 230 240 250
EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS KPLLSFSFGQ
260 270 280 290 300
SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG
310 320 330 340 350
LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD
360 370 380
QNFPLEPIED EKRDISTEGF CHLDDQNSEV KRARINPDS
Length:389
Mass (Da):43,832
Last modified:December 1, 2000 - v2
Checksum:i539C4CE41D2D8AEC
GO

Sequence cautioni

The sequence CAA63047 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133K → T in CAA63047 (PubMed:8600462).Curated1
Sequence conflicti266 – 267TA → PP in CAA63047 (PubMed:8600462).Curated2
Sequence conflicti388D → H in AAH25787 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048221135M → I.Corresponds to variant rs17825440dbSNPEnsembl.1
Natural variantiVAR_048222324M → L.Corresponds to variant rs6494dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91992 mRNA. Translation: CAA63047.1. Frameshift.
AC008044 Genomic DNA. Translation: AAF01478.1.
BC025787 mRNA. Translation: AAH25787.1.
CCDSiCCDS32127.1.
PIRiS64736.
RefSeqiNP_006011.2. NM_006020.2.
UniGeneiHs.94542.

Genome annotation databases

EnsembliENST00000216489; ENSP00000216489; ENSG00000100601.
GeneIDi8846.
KEGGihsa:8846.
UCSCiuc001xuc.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91992 mRNA. Translation: CAA63047.1. Frameshift.
AC008044 Genomic DNA. Translation: AAF01478.1.
BC025787 mRNA. Translation: AAH25787.1.
CCDSiCCDS32127.1.
PIRiS64736.
RefSeqiNP_006011.2. NM_006020.2.
UniGeneiHs.94542.

3D structure databases

ProteinModelPortaliQ13686.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114372. 1 interactor.
STRINGi9606.ENSP00000216489.

PTM databases

iPTMnetiQ13686.
PhosphoSitePlusiQ13686.

Polymorphism and mutation databases

BioMutaiALKBH1.

Proteomic databases

EPDiQ13686.
MaxQBiQ13686.
PaxDbiQ13686.
PeptideAtlasiQ13686.
PRIDEiQ13686.

Protocols and materials databases

DNASUi8846.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216489; ENSP00000216489; ENSG00000100601.
GeneIDi8846.
KEGGihsa:8846.
UCSCiuc001xuc.2. human.

Organism-specific databases

CTDi8846.
DisGeNETi8846.
GeneCardsiALKBH1.
H-InvDBHIX0011855.
HGNCiHGNC:17911. ALKBH1.
HPAiHPA044087.
MIMi605345. gene.
neXtProtiNX_Q13686.
OpenTargetsiENSG00000100601.
PharmGKBiPA134906996.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2731. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00390000004599.
HOGENOMiHOG000033905.
HOVERGENiHBG050487.
InParanoidiQ13686.
KOiK10765.
OMAiGFCHLDD.
OrthoDBiEOG091G0A10.
PhylomeDBiQ13686.
TreeFamiTF314609.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100601-MONOMER.

Miscellaneous databases

ChiTaRSiALKBH1. human.
GenomeRNAii8846.
PROiQ13686.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100601.
CleanExiHS_ALKBH1.
ExpressionAtlasiQ13686. baseline and differential.
GenevisibleiQ13686. HS.

Family and domain databases

Gene3Di2.60.120.590. 2 hits.
InterProiIPR004574. Alkb.
IPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR16557. PTHR16557. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00568. alkb. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB1_HUMAN
AccessioniPrimary (citable) accession number: Q13686
Secondary accession number(s): Q8TAU1, Q9ULA7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: November 30, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Detected in cytoplasm and nucleus when expressed as fusion protein with an N-terminal tag, or when the first 26 N-terminal residues are removed (PubMed:17979886 and PubMed:18603530). According to a report, the endogenous, unmodified protein localizes to mitochondria (PubMed:18603530). However, other studies report that it localizes primarily to the nucleus, which would be consistent with its DNA demethylase activity (PubMed:22961808).3 Publications

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.